The impact of infliximab treatment on quality of life in patients with inflammatory rheumatic diseases

In this study, we compare the health-related quality of life (HRQoL) of patients with moderate-to-severe rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), and study the effect of treatment with infliximab on the HRQoL of patients with these diseases. Short Form Health Survey-36 (SF-36) data from the placebo-controlled phases of 4 studies of infliximab in patients with inflammatory rheumatic diseases (n = 1990) were evaluated. Data came from the Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) (n = 428), the Safety Trial for Rheumatoid Arthritis with REMICADE Therapy (START) (n = 1083), the Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT) (n = 279), and the Infliximab Multinational Psoriatic Arthritis Clinical Trial II (IMPACT II) (n = 200). SF-36 assessments were made at weeks 0, 10, 30, and 54 in ATTRACT, weeks 0, 6, and 22 in START, weeks 0, 12, and 24 in ASSERT, and weeks 0 and 14 in IMPACT II. All patient populations had significantly impaired physical aspects of HRQoL at baseline relative to the general population of the United States, and the magnitude of impairment was similar across the diseases. Mean baseline physical component summary scores were 29 in the RA cohort, 32 in the PsA cohort, and 29 in the AS cohort. In all 3 diseases, patients who received infliximab showed significant improvement in physical component summary scores compared with those who received placebo. The magnitude of the difference of improvement (effect size, 95%CI) between infliximab and placebo groups was similar in the AS (10.1, 9.2–11.0), PsA (8.6, 7.8–9.4), and RA (10.1, 9.2–11.0) cohorts. Patients with RA and those with PsA treated with infliximab also showed greater improvement in the mental component summary score than those in the placebo group with an effect size of 4.6 (4.2–5.1) in RA and 2.7 (2.4–3.1) in PsA. Patients in large randomized controlled studies of infliximab in RA, PsA, and AS had similar impairment in physical aspects of HRQoL at baseline and showed significantly greater improvement in HRQoL after treatment with infliximab.     

Isolation and characterization of N98-1272 A, B and C, selective acetylcholinesterase inhibitors from metabolites of an actinomycete strain

A high throughput screening was carried out in order to search for inhibitors of acetylcholinesterase (AChE) from microorganism metabolites. An actinomycete strain was found to produce active compounds named N98-1272 A, B and C with IC50 of 15.0, 11.5, 12.5 microM, respectively. Structural studies revealed that the three compounds are identical to the known antibiotics, Manumycin C, B and A. Kinetic analyses showed that N98-1272 C (Manumycin A) acted as a reversible noncompetitive inhibitor of acetylcholinesterase, with a Ki value of 7.2 microM. The cyclohexenone epoxide part of the structure plays a crucial role in the inhibitory activity against AChE. Compared with Tacrine, N98-1272 A, B, and C exhibit much better selectivity toward AChE over BuChE.     

Tripeptidyl peptidase II promotes fat formation in a conserved fashion

Tripeptidyl peptidase II (TPPII) is a multifunctional and evolutionarily conserved protease. In the mammalian hypothalamus, TPPII has a proposed anti-satiety role affected by degradation of the satiety hormone cholecystokinin 8. Here, we show that TPPII also regulates the metabolic homoeostasis of Caenorhabditis elegans; TPPII RNA interference (RNAi) decreases worm fat stores. However, this occurs independently of feeding behaviour and seems to be a function within fat-storing tissues. In mammalian cell culture, TPPII stimulates adipogenesis and TPPII RNAi blocks adipogenesis. The pro-adipogenic action of TPPII seems to be independent of protease function, as catalytically inactive TPPII also increases adipogenesis. Mice that were homozygous for an insertion in the Tpp2 locus were embryonic lethal. However, Tpp2 heterozygous mutants were lean compared with wild-type littermates, although food intake was normal. These findings indicate that TPPII has central and peripheral roles in regulating metabolism and that TPPII actions in fat-storing tissues might be an ancient function carried out in a protease-independent manner.     

A strong constitutive ethylene-response phenotype conferred on Arabidopsis plants containing null mutations in the ethylene receptors <Emphasis Type="Italic">ETR1</Emphasis> and <Emphasis Type="Italic">ERS1</Emphasis>

Background  

The ethylene receptor family of Arabidopsis consists of five members, falling into two subfamilies. Subfamily 1 is composed of ETR1 and ERS1, and subfamily 2 is composed of ETR2, ERS2, and EIN4. Although mutations have been isolated in the genes encoding all five family members, the only previous insertion allele of ERS1 (ers1-2) is a partial loss-of-function mutation based on our analysis. The purpose of this study was to determine the extent of signaling mediated by subfamily-1 ethylene receptors through isolation and characterization of null mutations.     

Mass spectrometry-based strategies for characterization of histones and their post-translational modifications

Due to the intimate interactions between histones and DNA, the characterization of histones has become the focus of great attention. A series of mass spectrometry-based technologies have been dedicated to the characterization and quantitation of different histone forms. This review focuses on the discussion of mass spectrometry-based strategies used for the characterization of histones and their post-translational modifications.     

Arthrobacter terrae sp. nov., a psychrophilic actinobacterium with multi copies of capA gene isolated from Antarctic soil

A Gram-staining-positive, non-spore-forming, non-flagellated, ellipsoidal, strain Z1-20 ^T belonging to the genus Arthrobacter was isolated from a soil sample collected from the Zhongshan station, Antarctic. Phylogenetic analysis of the 16S rRNA gene sequences and phylogenetic analysis revealed that strain Z1-20 ^T formed a unique single cluster in the genus Arthrobacter and shared high 16S rRNA sequence similarities of 97.1% and 96.9% with A. glacialis HLT2-12-2 ^T and A. psychrochitiniphilus GP3^T, respectively. Values of Digital DNA-DNA hybridization (dDDH) between strain Z1-20 ^T against A. glacialis HLT2-12-2 ^T and A. psychrochitiniphilus GP3^T were 20.3% and 13.8%, respectively. Average nucleotide identity (ANI) score between strain Z1-20 ^T against A. glacialis HLT2-12-2 ^T and A. psychrochitiniphilus GP3^T were 72.5% and 72.1%, respectively. Genes for the synthesis of the osmoprotectant glycine betaine and higher copies of capA gene encoding cold shock protein were found in genome of Z1-20 ^T that may help Z1-20 ^T in cold-adaptation. Strain Z1-20 ^T comprised lysine as the diagnostic diamino acid. Based on the results of phylogenetic, phenotypic and chemotaxonomic features, strain Z1-20 ^T represents a novel species of a novel taxon of genus Arthrobacter, for which the name Arthrobacter terrae gen. nov., sp. nov. is proposed.

     

Oxidative stress protective function of ApY2SK2 dehydrin: a late embryogenesis abundant protein in embryogenic callus of Agapanthus praecox to promote post-cryopreservation survival

Dehydrins (DHNs) as the member of the late embryogenesis abundant protein family, play critical roles in seed dehydration protection and plant adaptation to multiple abiotic stresses. As an important method of germplasm preservation, cryopreservation is also an ideal research system to study compound stress. Oxidative stress, as the critical stress in cryopreservation, directly affects cell viability. Our previous in vitro tests indicated that ApY₂SK₂ DHN can effectively protect enzyme activity and almost double the survival rate of Arabidopsis thaliana seedlings after cryopreservation, but the in vivo protective effect of ApY₂SK₂ on cryopreservation have not yet been elucidated. In this study, ApY₂SK₂ type DHN was genetically transformed into embryogenic callus (EC) of Agapanthus praecox by overexpression (OE) and RNA interference (RNAi) techniques to evaluate the in vivo oxidative stress protective effect of DHNs during cryopreservation. The results showed that the cell viability had a completely opposite trend between OE and RNAi cell lines, and the cell relative death ratio of ApY₂SK₂-OE EC was significantly decreased 18.5% and ApY₂SK₂-RNAi cells was significantly increased 23.5% after cryopreservation. Overexpression ApY₂SK₂ increased non-enzymatic antioxidant (AsA and GSH) contents, antioxidant enzyme (POD and SOD) activities and up-regulated CAT, POD and GPX expression, while ApY₂SK₂-RNAi cells decreased CAT, FeSOD, POD and GPX expression during cryopreservation. These findings suggested that ApY₂SK₂ can affect ROS metabolism, alleviate H₂O₂ and OH·excessive generation, activate the antioxidant system, improve cellular REDOX balance and reduce membrane lipid peroxidation damage of plant cells during cryopreservation. DHNs can effectively improve cell stress tolerance and have great potential for in vivo or in vitro applications in plant cryopreservation.

     

Wheat TaANS-6D positively regulates leaf senescence through the abscisic acid mediated chlorophyll degradation in tobacco

Plant Growth Regulation - Anthocyanidin synthase (ANS) is involved in the synthesis of anthocyanins, which are important phytonutrients because of their beneficial effects on human health. Here, we...     

Plant Hormone Metabolome and Transcriptome Analysis of Dwarf and Wild-type Banana

Journal of Plant Growth Regulation - Gibberellin (GA), auxin (IAA) and brassinosteroid (BR) are indispensable in the process of plant growth and development. Currently, research on the regulatory...     

Hydrogen sulfide plays a potential alternative for the treatment of metabolic disorders of diabetic cardiomyopathy

Molecular and Cellular Biochemistry - Diabetic cardiomyopathy (DCM) is a cardiovascular complication that tends to occur in patients with diabetes, obesity, or insulin resistance, with a higher...